Synthesis and Biological Evaluation of 14‐Alkoxymorphinans. Part 10. 14‐O‐Methyl derivatives of 5‐methylnaltrexone and 5‐methylnaloxone

In several steps, 5, 14-O-dimethylnaltrexone (3) and 5, 14-O-dimethylnaloxone (4) were prepared starting from 5, 14-O-dimethyloxycodone (5). Compound 3 exhibited opioid agonism in vitro (guinea-pig ileum and mouse vas deferens preparations) and antagonism in vivo (AcOH-writhing test in mice), while compound 4 was found to be an agonist in vitro and in vivo.